After the initial transcription of tRNA precursor material from DNA, the material undergoes several enzymatic modifications before becoming functional tRNA molecules. We are interested in examining these modification processes to determine how they occur biochemically. In addition, we want to examine the effect of the loss of specific tRNA modifications on their functions. Although some modifications may be essential, and their loss would be lethal, there may be other functions which would alter cell growth without being lethal. We are particulary interested in obtaining mutants of Salmonella typhimurium of the latter class. One cell function that has already been shown to be affected by the loss of a pseudouridine modification of the tRNAHis is the regulation of the histidine biosynthetic enzymes. We are examining this, and other mutants, to determine what other pathways may have altered regulation. The characterization of such mutants should be useful for understanding how tRNA modifications occur and how they are involved in regulatory mechanisms.